慢性乙型肝炎病毒感染者中黄曲霉毒素暴露与肝癌发生关系的纵向研究

目的 研究慢性乙型肝炎病毒(HBV)感染者中黄曲霉毒素(AF)暴露与肝癌发生的关系.方法 在肝癌高发现场,对515例感染HBV的肝癌高危人群进行了21年定群纵向研究.结果 (1)观察人群肝癌人年发生率为1437.25/10万,极显著地高于相应自然人群的184.53/10万(P=0.000,RR=7.79),其他肿瘤两组问差异无统计学意义(P=0.576).(2)定期观察人群中发现的肝癌患者平均年龄较相应自然人群提前了1.4年,治后平均生存期延长了6.42个月.(3)AF暴露对象的肝癌人年发生率为2784.96/10万,极显著地高于非暴露人群的1251.02/10万(P=0.008,RR=2.23),其他肿瘤的发生率与AF暴露与否无关.(4)AF暴露人群肝癌发生率随着尿中AFM1排出量增加而上升,当24 h尿中AFM1排出量＞100 ng时,肝癌的人年发生率高达4717.82/10万.尿中AFM1排出量与肝功能异常明显相关(P=0.035),与HBeAg无明显相关性(P=0.812).(5)HBV感染同时伴有AF暴露人群的人年肝癌发病率(2784.96/10万)极显著地高于观察人群(P=0.001)和相应自然人群(P=0.000,RR=15.09).(6)诊断乙肝到肝癌发生的平均时间为14.65年,中位时间13.68年;诊断肝硬化到肝癌发生的平均时间为7.38年,中位时间6.40年.结论 HBV是肝癌发生的主要病因因素,AF暴露在肝癌的发生中具有明显的协同作用;定期观察肝癌高危人群能有效地实现早诊早治,提高疗效;防治肝炎和AF污染是预防肝癌的有效途径.

Longitudinal study of aflatoxin exposure in the development of primary liver cancer in patients with chronic hepatitis

Objective To study the relationship between aflatoxin exposure and the development of primary liver cancer (PLC) in patients with chronic hepatitis. Methods A 21-year longitudinal study was carried out in a large cohort of 515 PLC high-risk individuals with HBV infection in PLC high prevalence region. Results (1) The PLC year-incidence of cohort was 1437. 25/100 000. And it was significantly higher than that of the same natural peoples (184. 53/100,000, P = 0. 000, RR =7.79). There was no significant difference in the incidence of other tumors between these two groups (P =0.576). (2)The PLC patients in the cohort were diagnosed at an average age 1.4 year younger than those in the same natrural peoples and had an average survival of 6. 42 months longer than the latter. (3 ) The PLC year-incidence of those with the exposure to aflatoxin was significantly higher than that of unexposed people (2784. 96/100 000 vs 1251. 02/100 000, P = 0.008, RR =2.23). There was no relationship between the incidence rate of other tumors and the aflatoxin exposure. (4)The PLC year-incidence of aflatoxin-exposing people increased with the rising urine excretion of AFM,. When the urine excretion of AFM, was more than 100 ng during 24 hours, the PLC year-incidence was high as 4 717.82/100 000. The urine excretion of AFM, was also obviously related with the abnormal liver function ( P = 0.035 ). There was no relationship with the positive rate of HBeAg ( P = 0. 812). (5) The PLC year-incidence of those with the exposure to aflatoxin were infected with HBV (2 784. 96/100 000) significantly higher than that of cohort people (P =0. 001) and the same natural peoples ( P = 0. 000, RR = 15. 09). ( 6) It took an average time of 14. 65 years ( median 13.68) from hepatitis occurrence to PLC diagnosis and 7.38 years (median 6.40)from liver cirrhosis to PLC diagnosis.Conclusion HBV infection is a main etiological factor of PLC and the aflatoxin exposure has obvious synergistic effect in the carcinogenesis of PLC.Regular observation in a PLC high-risk cohort is effective for an early diagnosis and treatment.Hepatitis control and aflatoxin de-pollution is effective to inhibit the occurrence of PLC.